Vaccines for monkeypox disease and challenges in its production and distribution: a lesson from COVID-19 pandemic
Authors: Sakshi Watarkar, Prashant Upadhyay, Shankhaneel Ghosh, Aditya A. Godbole, Sai K. Kishori, Aroop Mohanty, Bijaya K. Padhi, Ranjit Sah
Journal: International Journal of Surgery (2023)

Monkeypox (MPX) is a zoonotic infection caused by a double-stranded DNA virus related to the smallpox virus and belongs to the Orthopoxvirus genus of the Poxviridae family. The monkeypox virus (MPXV) can be spread between people through respiratory droplets, direct skin-to-skin contact with bodily fluids, and contact with contaminated objects. It can also spread by contact with sick animals or their secretions. The present MPX outbreak is distinct in spreading quickly through sexual contact1,2. The first case of human MPX was reported in 1970 from the Democratic Republic of the Congo. Since then, the virus has spread to other African countries but rarely broken outside endemic areas. This situation changed in 2022 when the current multicountry MPX outbreak impacted more than 89 nations. WHO recently reported that cases had surpassed 79 000 globally3. A recent study published in The Lancet reported the first official case of reverse zoonosis, which is human-to-dog transmission, leading to the possibility of the virus circulating continuously among animal populations4. Up to now, there is no specific medicine or vaccine available for MPX. This makes the current situation more severe and pathetic, especially for the middle-income to low-income countries where healthcare resources are already exhausted and in crisis due to the recent coronavirus disease-2019 (COVID-19) pandemic outbreak. Vaccines can play a very important role in preventing MPX to become another pandemic from being a public health emergency of international concern (PHEIC) at present. With India's case toll rising to 20, we look into the country's vaccine distribution and virus control strategies to effectively prevent the spread of MPX5. Currently available potential vaccines and Indian Government guidelines for MPX As of today, there are no specific vaccines available for the prevention of MPX. Smallpox vaccine may give immunity against MPXV due to cross-reactivity and has proved to be 85% effective6. There are three vaccines currently available – ACAM2000, MVA-BN, and LC16 but they are not frequently used due to their associated adverse reactions7. ACAM2000 Developed using the cell culture technique, this vaccine was approved by the Food and Drug Administration (FDA) and licensed in the USA for smallpox and MPX for the population between 18 and 64. It is a live attenuated, replication-competent virus vaccine administered as a single dose by a scarification technique using a bifurcated needle, giving multiple skin inoculations. A booster dose can be given every 3 years to those exposed to high virulence strains and every 10 years to those exposed to low virulence strains of Orthopoxviruses. Injection site reactions, fever, malaise, headache, malaise, etc. are the common adverse reactions. Skin infections, eczema, and Stevens–Johnson syndrome have rarely been noted7. MVA-BN (JYNNEOS) It is a live attenuated, nonreplicating Ankara Vaccine licensed by the FDA for the prevention of smallpox and MPX. It is manufactured by Bavarian Nordic. It is given subcutaneously, two doses 28 days apart. Injection site reactions have been observed in greater than 1 in 10 vaccines. Vaccines might be ineffective in immunocompromised individuals7. LC16 A live attenuated, minimally replicating virus vaccine manufactured by KM Biologics. It has not been approved by the FDA for the prevention of MPX7. The Indian Central Government published guidelines for managing MPX in light of recent events. According to the recommendations, everyone who comes in contact with an infected person face-to-face, physically, or comes into contact with contaminated objects like clothing or bedding is considered a primary contact and is to be monitored for symptoms for 21 days. The contacts can remain in the same room, although they should isolate themselves in other rooms. They should ideally wear masks, practice good hand hygiene, and maintain social distancing8. Challenges in vaccine production and distribution Currently, there are two US FDA-approved live vaccines for MPX, of which only JYNNEOS have fewer complications. There is an utmost need to develop an effective vaccine specific to MPX that is either killed, mRNA vaccine, or viral vector vaccine7. Re-emergence of the MPXV is not throughout the geographic range. So, the new mechanisms of immune evasion and induction should be addressed while making vaccines9. Constant monitoring and development of newer vaccines are needed due to the occurrence of vaccine-associated complications causing increased morbidity and mortality. After the eradication of smallpox, its vaccination ceased thereby leaving 80% of the population unvaccinated. Thus, pharmaceutical companies cannot produce a vast number of smallpox vaccines immediately. Also, some vaccines require regular supplies such as influenza and now COVID-19 vaccines. After manufacturing, vaccines are then sent to packaging and storage facilities. Usually, these facilities are used to store different types of medicine and they are booked years in advance. So it may take time to develop the reserves of the smallpox vaccine. Also, the reproduction of the smallpox vaccine poses a great threat to the re-emergence of the smallpox disease. India is a conservative country where there is still a social stigma. So, it is only natural that the number of cases is low due to the disease mainly occurring in the homosexual or bisexual population. Researchers in India are aiming at indigenous production of a vaccine to limit our dependency on the JYNNEOS vaccine as its importation is not an option considering India's population and limited production capacity of JYNNEOS by the only manufacturer Bavarian Nordic India can manufacture 2.4 billion doses of vaccines annually. Still, problems arise with the storage, transportation, and distribution of vaccines in remote peripheral areas of the country due to their specific temperature and storage requirements. Although there was a cloud-based Co-WIN platform during the COVID-19 pandemic, India lacks a national vaccine delivery system integrated with immunization as public health is decentralized, and state governments are responsible for vaccine distribution10. India had low vaccine registration and administration rates during COVID-19 due to vaccine hesitancy, online registration for the vaccination, and misleading information spread by social media, promoting the need for vaccine awareness. In the United States, during previous emergencies (2009 swine flu and 2020 COVID-19) vaccines were distributed through Vaccine Tracking System run by Center for Disease Control which is integrated with state databases to track vaccinations and doses. But JYNNEOS is being broadcast from the Strategic National Stockpile which does not have any integration with state databases. Integrating the stockpile with Vaccine Tracking System would take months and requires more manpower. Overcoming the challenges during a public health emergency It is noteworthy that amidst a global public health emergency there arises a competition for vaccine production and distribution as evident during the COVID-19 pandemic in previous years11. High-income countries tend to stockpile the vaccines thus creating an acute shortage of vaccines in low-income to middle-income countries such that even frontline health workers were not able to get vaccinated during the COVID-19 pandemic12. In such a scenario, when the world is facing another health emergency in the form of MPX, it is of utmost importance that high-income countries with readily available resources work hand in hand with the lower-income to middle-income countries to tackle the situation efficiently. Vaccine donors and pharmaceutical companies must collaborate with clinicians, healthcare workers, and researchers in order to chalk out a methodical response plan11. Especially when it comes to the MXPV situation, high-income countries should learn a lesson from the COVID-19 pandemic that it is pointless to compete for vaccines and treatments but is beneficial to work together with other countries on a global scale11, so that there is a fair distribution and management of resources. Conclusion and recommendations The Center's guidelines state that the infected individual should wear a triple-ply mask, and infective skin lesions should be covered as much as possible to reduce the chance of contact with others. According to the available data, there is no specific vaccination for MPX yet. Although it is seen that smallpox vaccines are effective against MPXV, it is noteworthy that not many people are immunized since its administration ceased after the disease eradication in the 1980s13. However, any vaccination that satisfies the WHO requirements for potency, purity, and stability can be used to stop the expected outbreak. In order to stop the continuous spread of MPX, the WHO recommends using active surveillance, quick case and contact identification, and appropriate isolation instead of mass vaccination. It is recommended to keep patients isolated until all lesions have healed and the scabs have wholly peeled off. Asymptomatic contacts should also be prohibited from giving blood, cells, tissues, organs, or semen while being monitored8. Additionally, extensive research should be encouraged to develop newer vaccines using advanced molecular techniques on an international scale to repurpose similar disease vaccines for MPX. International collaboration and universal support should be encouraged for this, in order to prevent vaccine shortages in the future, for example, companies currently holding the license to vaccine production should be encouraged to make new licensing deals with other producers to ensure vaccine manufacturing and distribution globally14. With international coordination, the MPX health emergency could be tackled effectively. Ethical approval None. Sources of funding No funding was received. Author contribution S.W., P.U., S.G., A.A.G., and S.K.K. designed and drew the original draft. A.M., B.K.P., and R.S. reviewed the literature and critically edited the article. All authors read and approved the final version of the manuscript. Conflicts of interest disclosure None. Research registration unique identifying number (UIN) None. Guarantor Ranjit Sah.